The program is concerned with certain aspects of metabolic regulation in mamalian organisms. The following are areas of investigation. (1) The mediation of hormone effects by cyclic adenylate, (2) Cyclic adenylate metabolism, (3) Cyclic guanylate metabolism and action (in smooth muscle, sperm, lung and liver), (4) The actions of insulin, (5) The molecular mechanism of insulin action, (6) The control of gluconeogenesis and glycogenolysis, (7) The characterization and regulation of protein kinases, (8) Plasma membrane and receptors, (9) Glucose, ion, and beta-hydroxybutyrate transport, (10) Function and chemical anatomy of the (Na ion plus K)-ATPase, (11) Synthesis and metabolism of pulmonary surfactant, (12) Source, nature and role of lipoprotein lipase and other lipases in fat transport, (13) Characterization of phosphodiesterases and development of compounds for their regulation, (14) Role of cyclic nucleotides in smooth muscle contractility, (15) Role of cyclic nucleotides in cardiac contractility and metabolism, (16) Metabolic defects in hereditary obesity and diabetes in mice, (17) Phosphorylation of glycogen synthetase, (18) Phosphoprotein phosphatases, (19) Characterization and control of adenylate cyclase, (20) Control of cell growth in culture, (21) Mechanism and mediation of gamma-adrenergic function and cholinergic function, (22) Control of amino acid mobilization from muscle, (23) Effects of glucagon, insulin and somatostatin on glucose metabolism in dogs.